Saner-Amigh Karla, Mayhew Bobbie A, Mantero Franco, Schiavi Francesca, White Perrin C, Rao Chalama V, Rainey William E
Department of Physiology, Medical College of Georgia, 1120 15th Street, Augusta, Georgia 30912, USA.
J Clin Endocrinol Metab. 2006 Mar;91(3):1136-42. doi: 10.1210/jc.2005-1298. Epub 2005 Dec 6.
The mechanisms driving steroid production in aldosterone-producing adenomas (APAs) are poorly defined. However, previous studies have shown that steroid production in some cortisol-producing adenomas is regulated by aberrant expression of G protein-coupled receptors. Aberrant adrenal expression of LH receptors has been shown to cause Cushing's syndrome, but the role of LH receptors in Conn's disease (hyperaldosteronism) has not been studied.
The objective of the study was to determine whether APAs express elevated LH receptor, compared with normal adrenal (NA).
Pools of RNA from NA and APAs were hybridized to oligonucleotide microarrays. Data were confirmed using real-time RT-PCR analysis of RNA derived from NA (n = 20) and APAs (n = 18). Aldosterone synthase transcription was studied in H295R adrenocortical cells transfected with an LH receptor expression construct and reporter constructs prepared from CYP11B2 5'-flanking DNA.
The patient population consisted of 20 normal control adrenals and 18 adenomas from patients with APAs.
Regulation of CYP11B2 gene expression by aberrant LH receptor expression in aldosterone-producing adrenal adenoma was measured.
LH/choriogonadotropin receptor gene and CYP11B2 are indicated as having greater than 25-fold expression in one pool of APA mRNA samples over NA using microarray analysis. Real-time RT-PCR analyses indicated that one APA sample (APA-LH receptor) exhibited more than 2400-fold elevation in LH receptor expression over NA. Examination of LH receptor mRNA levels in 18 independent APA samples indicated elevated expression in nine samples when compared with NA. In H295R cells transfected with LH receptor, LH treatment caused a concentration-dependent increase in CYP11B2 reporter activity.
LH receptor expression is elevated in many APAs, which makes LH a potential cause of the excessive production of aldosterone in a subset of these adrenal tumors.
醛固酮瘤（APA）中驱动类固醇生成的机制尚不清楚。然而，先前的研究表明，一些皮质醇瘤中的类固醇生成受G蛋白偶联受体异常表达的调节。促黄体生成素（LH）受体在肾上腺的异常表达已被证明可导致库欣综合征，但LH受体在原发性醛固酮增多症（Conn病）中的作用尚未得到研究。
本研究的目的是确定与正常肾上腺（NA）相比，APA中LH受体表达是否升高。
将来自NA和APA的RNA池与寡核苷酸微阵列杂交。使用来自NA（n = 20）和APA（n = 18）的RNA进行实时逆转录-聚合酶链反应（RT-PCR）分析来确认数据。在转染了LH受体表达构建体和由CYP11B2 5'-侧翼DNA制备的报告基因构建体的H295R肾上腺皮质细胞中研究醛固酮合酶转录。
患者群体包括20个正常对照肾上腺和18个来自APA患者的腺瘤。
测定醛固酮生成性肾上腺腺瘤中异常LH受体表达对CYP11B2基因表达的调节作用。
使用微阵列分析表明，在一组APA mRNA样本中，LH/绒毛膜促性腺激素受体基因和CYP11B2的表达比NA高25倍以上。实时RT-PCR分析表明，一个APA样本（APA-LH受体）的LH受体表达比NA高2400倍以上。对18个独立APA样本中LH受体mRNA水平的检测表明，与NA相比，9个样本中的表达升高。在转染了LH受体的H295R细胞中，LH处理导致CYP11B2报告基因活性呈浓度依赖性增加。
许多APA中LH受体表达升高，这使得LH成为这些肾上腺肿瘤中一部分醛固酮过度产生的潜在原因。
